The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.

Plasma electron acceleration driven by a long-wave-infrared laser.

Laser-driven plasma accelerators provide tabletop sources of relativistic electron bunches and femtosecond x-ray pulses, but usually require petawatt-class solid-state-laser pulses of wavelength λL ~ 1 µm. Longer-λL lasers can potentially accelerate higher-quality bunches, since they require less power to drive larger wakes in less dense plasma. Here, we report on a self-injecting plasma accelerator driven by a long-wave-infrared laser: a chirped-pulse-amplified CO2 laser (λL ≈ 10 µm). Through optical scattering experiments, we observed wakes that 4-ps CO2 pulses with < 1/2 terawatt (TW) peak power drove in hydrogen plasma of electron density down to 4 × 1017 cm-3 (1/100 atmospheric density) via a self-modulation (SM) instability. Shorter, more powerful CO2 pulses drove wakes in plasma down to 3 × 1016 cm-3 that captured and accelerated plasma electrons to relativistic energy. Collimated quasi-monoenergetic features in the electron output marked the onset of a transition from SM to bubble-regime acceleration, portending future higher-quality accelerators driven by yet shorter, more powerful pulses.

Robotic-assisted versus laparoscopic incisional hernia repair: a systematic review and meta-analysis.

PURPOSE: This study aimed to perform a systematic review and meta-analysis comparing the efficacy and safety outcomes of robotic-assisted and laparoscopic techniques for incisional hernia repair. METHODS: PubMed, Embase, Scopus, Cochrane databases, and conference abstracts were systematically searched for studies that directly compared robot-assisted versus laparoscopy for incisional hernia repair and reported safety or efficacy outcomes in a follow-up of ≥ 1 month. The primary endpoints of interest were postoperative complications and the length of hospital stay. RESULTS: The search strategy yielded 2104 results, of which four studies met the inclusion criteria. The studies included 1293 patients with incisional hernia repairs, 440 (34%) of whom underwent robot-assisted repair. Study follow-up ranged from 1 to 24 months. There was no significant difference between groups in the incidence of postoperative complications (OR 0.65; 95% CI 0.35-1.21; p = 0.17). The recurrence rate of incisional hernias (OR 0.34; 95% CI 0.05-2.29; p = 0.27) was also similar between robotic and laparoscopic surgeries. Hospital length of stay (MD - 1.05 days; 95% CI - 2.06, - 0.04; p = 0.04) was significantly reduced in the robotic-assisted repair. However, the robot-assisted repair had a significantly longer operative time (MD 69.6 min; 95% CI 59.0-80.1; p < 0.001). CONCLUSION: The robotic approach for incisional hernia repair was associated with a significant difference between the two groups in complications and recurrence rates, a longer operative time than laparoscopic repair, but with a shorter length of stay.

Stable Positron Acceleration in Thin, Warm, Hollow Plasma Channels.

Hollow plasma channels are attractive for lepton acceleration because they provide intrinsic emittance preservation regimes. However, beam breakup instabilities dominate the dynamics. Here, we show that thin, warm hollow channels can sustain large-amplitude plasma waves ready for high-quality positron acceleration. We verify that the combination of warm electrons and thin hollow channels enables positron focusing structures. Such focusing wakefields unlock beam breakup damping mechanisms. We demonstrate that such channels emerge self-consistently during the long-term plasma dynamics in the blowout's regime aftermath, allowing for experimental demonstration.

Producing multi-coloured bunches through beam-induced ionization injection in plasma wakefield accelerator.

This paper discusses the properties of electron beams formed in plasma wakefield accelerators through ionization injection. In particular, the potential for generating a beam composed of co-located multi-colour beamlets is demonstrated in the case where the ionization is initiated by the evolving charge field of the drive beam itself. The physics of the processes of ionization and injection are explored through OSIRIS simulations. Experimental evidence showing similar features are presented from the data obtained in the E217 experiment at the FACET facility of the SLAC National Laboratory. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Betatron radiation and emittance growth in plasma wakefield accelerators.

Beam-driven plasma wakefield acceleration (PWFA) has demonstrated significant progress during the past two decades of research. The new Facility for Advanced Accelerator Experimental Tests (FACET) II, currently under construction, will provide 10 GeV electron beams with unprecedented parameters for the next generation of PWFA experiments. In the context of the FACET II facility, we present simulation results on expected betatron radiation and its potential application to diagnose emittance preservation and hosing instability in the upcoming PWFA experiments. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Decay and persistence of empty bivalve shells in a temperate riverine system.

Bivalve shells can persist over a geological time, acting as important physical resources to the associated fauna. However, few studies have investigated their relevance as persistent long-term ecological attributes to the ecosystem. As such, it is relevant to investigate the shell decays in riverine systems subjected to different environmental conditions. Towards this end, shells of four bivalve species (Anodonta anatina, Corbicula fluminea, Potomida littoralis and Unio delphinus) were made available individually and in clusters of different sizes. The effects of river flow and seasonality were assessed by recording the decay rates of shells in lentic and lotic habitats throughout the year. Our results evidenced that the decays varied among species and depend on shell size, water flow and season. Thin shelled species (A. anatina and U. delphinus) showed the highest mean percentage of decay per month, 3.17% (lotic) and 2.77% (lotic), respectively, and thick shelled species (C. fluminea and P. littoralis) the lowest, 2.02% (lotic) and 1.83% (lotic), respectively. Size was a relevant variable explaining decays, with the smallest shells presenting the highest values, 1.2-2.0 times higher compared to the other size classes. Also, robustness showed to be the most relevant feature explaining the decays in thick shelled species. River flow was also a relevant descriptor of the decays, with higher decays observed in the lotic compared to the lentic habitats. Furthermore, lower decays were observed mainly during summer (lentic site), and autumn (lotic site) associated to the burial effect of leaves. In summary, shells of the native species A. anatina and U. delphinus are expected to persist and contribute less as habitat engineering species, than shells of the native P. littoralis and invasive C. fluminea species. This is especially valid to lotic habitats where the decays were up to 2.13 times higher than in lentic habitats.

Stroke in systemic lupus erythematosus and antiphospholipid syndrome: risk factors, clinical manifestations, neuroimaging, and treatment.

Neurologic disorders are among the most common and important clinical manifestations associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), mainly those that affect the central nervous system (CNS). Risk of cerebrovascular events in both conditions is increased, and stroke represents one of the most severe complications, with an incidence rate between 3% and 20%, especially in the first five years of diagnosis. This article updates the data regarding the risk factors, clinical manifestations, neuroimaging, and treatment of stroke in SLE and APS.

Observation of Betatron X-Ray Radiation in a Self-Modulated Laser Wakefield Accelerator Driven with Picosecond Laser Pulses.

We investigate a new regime for betatron x-ray emission that utilizes kilojoule-class picosecond lasers to drive wakes in plasmas. When such laser pulses with intensities of ∼5×10^{18} W/cm^{2} are focused into plasmas with electron densities of ∼1×10^{19} cm^{-3}, they undergo self-modulation and channeling, which accelerates electrons up to 200 MeV energies and causes those electrons to emit x rays. The measured x-ray spectra are fit with a synchrotron spectrum with a critical energy of 10-20 keV, and 2D particle-in-cell simulations were used to model the acceleration and radiation of the electrons in our experimental conditions.

Lattice Location of Mg in GaN: A Fresh Look at Doping Limitations.

Radioactive ^{27}Mg (t_{1/2}=9.5 min) was implanted into GaN of different doping types at CERN's ISOLDE facility and its lattice site determined via ß^{-} emission channeling. Following implantations between room temperature and 800 °C, the majority of ^{27}Mg occupies the substitutional Ga sites; however, below 350 °C significant fractions were also found on interstitial positions ∼0.6 Å from ideal octahedral sites. The interstitial fraction of Mg was correlated with the GaN doping character, being highest (up to 31%) in samples doped p type with 2×10^{19} cm^{-3} stable Mg during epilayer growth, and lowest in Si-doped n-GaN, thus giving direct evidence for the amphoteric character of Mg. Implanting above 350 °C converts interstitial ^{27}Mg to substitutional Ga sites, which allows estimating the activation energy for migration of interstitial Mg as between 1.3 and 2.0 eV.

Role of Direct Laser Acceleration of Electrons in a Laser Wakefield Accelerator with Ionization Injection.

We show the first experimental demonstration that electrons being accelerated in a laser wakefield accelerator operating in the forced or blowout regimes gain significant energy from both the direct laser acceleration (DLA) and the laser wakefield acceleration mechanisms. Supporting full-scale 3D particle-in-cell simulations elucidate the role of the DLA of electrons in a laser wakefield accelerator when ionization injection of electrons is employed. An explanation is given for how electrons can maintain the DLA resonance condition in a laser wakefield accelerator despite the evolving properties of both the drive laser and the electrons. The produced electron beams exhibit characteristic features that are indicative of DLA as an additional acceleration mechanism.

Adição da proteína específica do oviduto de porcas (pOSP) e da melatonina em meios de maturação e o efeito na clivagem in vitro de embriões suínos / Addition of the oviduct specific protein of porcine (pOSP) and melatonin in maturation media and their effect on the in vitro production of pig embryos

No presente estudo, utilizou-se a melatonina e a proteína específica do oviduto (pOSP) nos meios de maturação in vitro. Foram avaliadas a expansão do complexo cumulus-ovócito (CCOs), as concentrações intracelulares de espécies reativas de oxigênio (ROS) e o desenvolvimento embrionário nos diferentes grupos (C = controle; T1 = somente com melatonina; T2 = com melatonina e pOSP e T3 somente com pOSP). No tocante à expansão do CCOs, houve diferença (P<0,05) dos valores obtidos no grupo C em relação aos valores médios dos grupos T1, T2 e T3, porém não houve diferença entre os valores obtidos nos tratamentos (P>0,05). Na dosagem de ROS, não houve diferença entre os valores médios obtidos no grupo C (26,4±10,9) e o valor verificado no grupo T1 (23,4±7,8), porém no grupo T2 (21,3±9,7) o valor médio mostrou-se satisfatório em relação ao valor do grupo C. No entanto, o valor médio do grupo T3 (16,6±10,5) foi o que demonstrou resultado mais satisfatório quando comparado aos demais grupos (P<0,05). A produção de embriões foi avaliada por meio da taxa de clivagem. Não houve diferença (P >0,05) entre os valores obtidos entre o grupo C (48,9 %) e os valores verificados nos grupos T1 (51,5 %), T2 (50 %), T3 (57,7 %), nem destes entre si. Este estudo permitiu concluir que a proteína específica do oviduto recombinante e a melatonina foram eficientes em melhorar a expansão dos CCOs. Além disso, as células tratadas com pOSP mostraram-se com menor quantidade de ROS, podendo a pOSP ser considerada um antioxidante proteico.(AU)

The present study used melatonin and recombinant oviduct specific protein (pOSP) in in vitro maturation medium (IVM). The expansion of the cumulus-oocyte complexes (COCs), the intracellular concentrations of reactive oxygen species (ROS) and embryo development of the different groups were evaluated (C = control; T1 = melatonin; T2 = melatonin and pOSP and T3 = pOSP). Regarding the COCs expansion, the groups T1, T2 and T3 showed satisfactory results compared with group C (P<0.05), but there was no difference between treatments (P>0.05). In the ROS dosage, there was no difference between the mean values obtained in group C (26.4 ± 10.9) and group 1 (23.4 ± 7.8). However, in group 2 (21.3 ± 9.7), the average value was found to be satisfactory in relation group C. Despite that, the average value of treatment 3 (16.6 ± 10.5) was the most satisfactory result found compared to the other groups (P<0.05). The production of embryos was evaluated by cleavage rate, there was no difference between the values obtained in group C and the values recorded in groups T1 (51.5 %), T2 (50 %), T3 (57.7 %), and among them. This study showed that the pOSP and the melatonin were effective in the improvement of the expansion of COCs cells. In addition, the cells that were treated with pOSP presented a lower amount of ROS, allowing the pOSP to be considered a proteic antioxidant.(AU)

Effects of poor hygiene on cytokine phenotypes in children in the tropics.

We describe immune phenotypes (innate and adaptive cytokines) according to environmental exposure using latent class analysis. A total of 310 schoolchildren living in Ecuador were assayed for spontaneous cytokine production as well as mitogen (SEB)-stimulated cytokines in whole blood cultures. We collected data on environmental exposures by questionnaire and on intestinal parasites by examination of stool samples. Latent class analysis (LCA) was used to group children according to their innate (IL-6, IL-8, IL-10 and TNF-α) and adaptive (IL-5, IL-13, IL-17, IFN-γ and IL-10) cytokine profile. We also conducted multiple-group LCA and LCA with covariates to evaluate the effect of predictors on profile membership. We identified both hyporesponsive and Th2-modified immune phenotypes produced by peripheral blood leukocytes (PBLs) that were associated with intestinal worms and birth order, providing insights into how poor hygiene mediates immunologic effects on immune-mediated diseases.

Influência da condição corporal ao parto no balanço energético e desempenho reprodutivo de cabras leiteiras no pós-parto / Influence of body condition at calving on energy balance and reproductive performance of dairy goats in the postpartum

O estudo teve como objetivo avaliar a influência da condição corporal (CC) ao parto no balanço energético (BE) e o desempenho reprodutivo de cabras Alpinas no pós-parto. Foram utilizadas 68 cabras distribuídas em três grupos (G), sendo: G1- cabras com baixa CC (CC entre 1,5 e 2,5); G2: cabras com moderada CC (entre 2,75 e 3,5) e G3: cabras com alta CC (entre 3,75 e 5,0). Os animais receberam dieta (silagem de milho e concentrado, com 18% de proteína bruta e 1,7Mcal/kg de matéria seca de energia líquida) ad libitum. As avaliações foram feitas nas oito primeiras semanas de lactação, para determinação do BE, do intervalo do parto à primeira ovulação e ao primeiro estro e da concentração plasmática de progesterona. Os dados foram analisados por análise de variância a 5% de probabilidade. Não houve efeito da CC ao parto sobre o BE dos animais. Todas as cabras apresentaram BE negativo ao parto, com mudança para BE positivo aos 51, 58 e 64 dias pós-parto, respectivamente. Não houve diferença na concentração plasmática de progesterona nos três grupos, sendo caracterizada função luteal (concentração ≥1ng/dL) em apenas 5,9% dos animais avaliados. O intervalo do parto à primeira ovulação foi de 46 dias. Apenas 4,4% das cabras exibiram estro. Cabras leiteiras de média produção, entre 2,5 e 3,0kg de leite/dia, entram em BE negativo ao parto, independentemente da CC apresentada, influenciando negativamente o reinício da atividade ovariana no pós-parto.(AU)

The concentration of progesterone in the blood was used to study the effect of body condition score (BCS) on the post-partum ovarian activity of dairy goats. Sixty-eight female goats were distributed between three treatments. Treatment 1: goats with BCS between 1.00 and 2.75; Treatment 2: goats with BCS between 2.75 and 3.50; and Treatment 3: goats with BCS between 3.50 and 5.00. The goats had the blood collected immediately after birth, and from that time up to the eighth week post-partum at three day intervals. The progesterone analysis on the blood was used to determine the interval between the birth and the first ovulation. The females were teasing two times per day for estrus detection and determination of the time interval from birth to first estrus. No significant difference was found on the progesterone concentration between treatments. The luteal functionality was characterized in only 5.9% of goats, with a concentration higher than 1ng/mL. The period from birth to first ovulation was 46 days. The detectable estrus was found in only 4.4% of goats. The BCS at birth did not influence the recovery of ovarian activity of dairy goats.(AU)

Expressão gênica em ovócitos suínos de diferentes classificações morfológicas / Gene expression in swine oocytes in different morphological classifications

A produção in vitro de embriões suínos tem alcançado resultados insatisfatórios: ovócitos maturados in vivo produzem uma porcentagem maior de embriões em relação aos maturados in vitro. O sucesso da maturação in vitro está diretamente relacionado com a competência ovocitária. Somente ovócitos competentes são capazes de serem fecundados e terem desenvolvimento embrionário normal. A competência ovocitária pode ser avaliada por vários parâmetros. Recentemente têm sido utilizados como parâmetro os estudos da expressão de genes associados com a competência. O presente trabalho teve por objetivo avaliar diferenças na expressão dos genes BMP15, RYBP, MATER e ZAR1 em ovócitos imaturos de diferentes classes morfológicas, sendo elas: 1, 2, 3 e 4, com a finalidade de proporcionar importantes marcadores moleculares relacionados com a capacidade ovocitária. O RNA total dos ovócitos foi extraído e utilizado como molde para a síntese da primeira fita de cDNA. Os resultados da expressão gênica foram analisados utilizando-se modelo misto, considerando os dados de expressão gênica variável dependente e as classes ovocitárias variáveis independentes. Os genes BMP15, ZAR1 e RYBP apresentaram expressão semelhante nas classes ovocitárias 1, 2 e 3; somente a categoria 4 diferiu na expressão desses genes (P<0,05). O gene MATER foi expresso de forma semelhante em todas as classes ovocitárias estudadas (P>0,05). A técnica de RT-qPCR foi eficiente para detecção desses transcritos em ovócitos de diferentes classes. No entanto, para melhor entendimento do envolvimento desses transcritos na aquisição da competência ovocitária, são necessários mais estudos avaliando ovócitos de diferentes classes morfológicas, em diferentes fases de desenvolvimento, e implicação de outros genes envolvidos com a competência ovocitária.

The in vitro production of pig embryos has achieved unsatisfactory results; in vivo matured oocytes produce a higher percentage of embryos compared to in vitro maturation. The success of in vitro maturation is directly related to oocyte competence. Only competent oocytes are capable of being fertilized and have normal embryonic development. The oocyte competence can be assessed using several parameters. Recently these parameters have been used for gene expression studies associated with competence. This work aimed to evaluate differences in gene expression BMP15, RYBP, MATER, ZAR1 as endogenous control and the constitutive gene GAPDH in immature oocytes of different morphological classes which are: 1, 2, 3 and 4, in order to provide significant molecular markers linked to the ability of development. Oocytes Total RNA was extracted and used as a template for synthesis of the first cDNA strand. The results of gene expression were analyzed using a mixed model, considering the dependent gene expression data and independent ovocitary variable classes. The genes BMP15, RYBP ZAR1 and showed similar ovocitary expression in classes 1, 2 and 3 differ only in category 4 in their expression (P<0.05). The MATER gene was similarly expressed in all ovocitary classes studied (P>0.05). The RTQ-PCR technique was effective for detection of these transcripts in oocytes from different classes. However, for better understanding of the involvement of these transcripts in the acquisition of oocyte competence more studies are needed to evaluate different morphological classes of oocytes at different stages of development and the implication of other genes involved in oocyte competence.

Influência do Hormônio do Crescimento na concentração de testosterona plasmática e nas características seminais de touros jovens e adultos da raça Nelore / Influence of Growth Hormone on plasma testosterone concentration and seminal characteristics of young and adult Nellore bulls

Estudou-se o efeito do Hormônio do Crescimento bovino (bGH) sobre os parâmetros seminais e a concentração sérica de testosterona de touros da raça Nelore. Dezesseis touros foram distribuídos em um delineamento fatorial 2 x 2 (duas idades e dois níveis de r-bST), com quatro animais em cada tratamento. As aplicações de r-bST foram realizadas a cada 14 dias, totalizando nove aplicações por animal, em um período experimental de 120 dias. As coletas de sêmen foram realizadas a cada 15 dias e, para determinar as concentrações de testosterona, foram realizadas coletas de sangue a cada quatro horas, num total de 24 horas, e a cada 30 dias a partir da primeira aplicação de r-bST. O sêmen dos touros adultos tratados com r-bST apresentaram maior motilidade e vigor (P<0,05) em relação aos animais controles (79,70±11,56% vs 64,06±23,65%) e (3,80±0,88 vs 2,92±1,25), respectivamente; entretanto, as demais características seminais não foram influenciadas (P>0,05) pelo tratamento com r-bST. Os aspectos físicos do sêmen dos touros jovens não foram afetados (P>0,05) pelo tratamento com r-bST. Entretanto o tratamento com r-bST diminuiu os defeitos morfológicos menores (delgado, gigante normal, pequeno normal, globoso, cabeça isolada normal, abaxial, cauda dobrada e enrolada levemente e gota distal) em relação aos jovens não tratados (P<0,05). As concentrações séricas de testosterona foram influenciadas (P<0,05) pelo tratamento, aos 120 dias após a primeira aplicação do r-bST, e apresentaram tendência de três picos no período de 24 horas.

The aim of this trial was to study the effect of Growth Hormone (GH) on the seminal parameters and testosterone profile from Nellore bulls. Sixteen bulls were allocated in a 2 x 2 factorial arrangement (two ages and two r-bST levels), with four animals per treatment. The r-bST was injected every 14 days, with a total of nine injections per animal, during the 120 days of the experimental period. The semen collections were done every 15 days and blood samples were collected in four hour intervals for 24 hours, and in 30 day intervals from the first r-bST injection for testosterone profile. The semen of adult bulls treated with r-bST showed greater MOT and VIG (P<0.05) in relation to the control (79.70±11.56% vs 64.06±23.65%) and (3.80±0.88 vs 2.92±1.25) respectively; however, the other evaluated seminal parameters were not affected (P>0.05) by the r-bST treatment. The physical measurements of the semen of young animals was also unaffected (P>0.05) by r-bST injection. However, the treatment with r-bST decreased the number of minor morphologic defects (narrow head, giant head, small normal head, round head, free normal head, abaxial implantation, simple bent tail and distal droplet) compared to untreated young bulls (P<0.05). The serum testosterone concentration was influenced (P<0.05) by treatment, at 120 days after the first injection of r-bST and they showed a tendency of three picks in a 24 hour period of sampling.

Follicular dynamics and gene expression in granulosa cells, corpora lutea and oocytes from gilts of breeds with low and high ovulation rates.

Follicular dynamics and the expression of candidate genes using real-time polymerase chain reaction (PCR) were compared during the oestrous cycle of pig breeds with high (commercial line; n=24) and low (local Brazilian Piau; n=21) ovulation rates and prolificacy. Gilts were killed on Days 0, 4, 10 and 18 of the oestrous cycle and visible ovarian follicles were classified by follicular diameter. Recovered cumulus-oocyte complexes were classified as normal or atretic and frozen in liquid nitrogen until RNA extraction. Low ovulation rates and/or prolificacy in Piau gilts was associated with a different pattern of follicle development, with lower numbers of small follicles on Day 18, fewer large follicles on Days 0 and 18 (P≤0.05) and a higher proportion of atretic follicles on Days 0 and 18 (P≤0.05). Compared with commercial line gilts, less-prolific Piau gilts exhibited higher expression of apoptotic genes during luteolysis (CASP3 and FASL; P≤0.05), decreased expression of TGFBR2 and BAX mRNA in the corpus luteum (P≤0.05), higher expression of apoptotic genes (FAS, BCL2 and CASP8; P≤0.05) in granulosa cells and a greater abundance (P≤0.05) of genes controlling oocyte-secreted factors (GDF9, BMP15 and BMP6), suggesting underlying mechanisms controlling differences in follicular development, ovulation rate and inherent prolificacy in this pig breed.